In Vitro Bioactivity in ToxCast Assays for Fruit and Vegetable Extracts

The ToxCast and Tox21 programs have generated in vitro screening data for over 1000 chemicals to aid in hazard identification and setting chemical testing priorities. These data, together with high-throughput pharmacokinetic data, are used to infer possible toxic responses and external concentrations required to elicit these effects. There is only

limited experience in evaluating dose-response for natural products in these assays. In this study, juices were extracted from 30 organically grown fruits and vegetables. These juices were screened in concentration-response format across primary human cell and co-culture assays (BioMAP systems) to assess similarities of pathway responses of the extracts with those of database compounds. Bioactivities noted with unpeeled potato juice were immunomodulatory and tissue remodeling activities across endothelial, peripheral blood mononuclear and fibroblast

cells. This pattern of response was similar to quercetin, a plant-derived flavonoid. Broccoli juice initiated anti-proliferative effects on endothelial, fibroblast and smooth muscle cells with significant similarity to mitomycin C (374 ng/mL; Pearson, r=0.806) and the fungicide mancozeb (40 μM; Pearson, r=0.776). To relate in vitro concentrations to

administered dose, the filtered juice yield per g item was used with the plasma volume of a 70kg adult to approximate % juice present in systemic circulation after eating. This value was used as a surrogate for target tissue concentration. The activity described for broccoli was elicited at 0.5%, the amount of juice anticipated in the circulation following consumption of 2 cups of broccoli. Importantly, the bioactivities noted do not necessarily lead to adverse effects. These data provide context for assessing the in vivo relevance of in vitro concentration-response and

bioactivity data generated in ToxCast and similar screening programs. This abstract does not necessarily reflect EPA policy.